efficacy and safety study of dcb-ad1 in patients with mild to moderate alzheimer's disease

Conditions: Dementia, Alzheimer Type

Summary: a double-blind, randomized, placebo controlled study to evaluate the efficacy and safety of dcb-ad1 in patients with mild to moderate alzheimer's disease. because of the limitation of the sample size we could expect but a positive trend of the efficacy unless the effect size of dcb-ad1 is larger than 0.63. this information will provide us clue if further clinical investigation such as a phase iii study should be carried out in an even larger scale. we also should be able to obtain valuable experience on the adverse effect of prolonged (24-week) use of fo-ti.

the growing number of patients with dementia has become a great concern of many aging societies. up to this moment no treatment can stop alzheimer's dementia (ad), thus, developing new treatments are still mandatory. in this study we will investigate a new drug dcb-ad1, an herbal medicine derived from root of fo-ti. historically the chinese used the fo-ti root for its rejuvenating properties to treat premature aging, weakness and so on. in dcb (development center of biotechnology)'s preliminary studies using human neuroblastoma cell, sk-n-sh, fo-ti water extracts exhibited high potential in preventing a-beta and hydrogen peroxide-induced cell death. from two different ad animal models, dcb have observed neuroprotection effects of fo-ti using water maze and hole-board exploration tests, though the pharmacological effect of fo-ti has yet been clarified, its protective effect may result from radical scavenging activities, anti-inflammatory effect or anti-peroxidation. we intend to investigate dcb-ad1 on its cognitive and neurophysiological effects on alzheimer disease through a randomized, double-blind, placebo-controlled therapeutic trial for 24 weeks. we will complete 80 eligible cases for analysis in this clinical trial with 40 in each investigation site. the estimated drop-out rate is around 25\~30 %. patients are eligible if they fulfill criteria for a diagnosis of probable ad of nincds-adrda. we will include patients with mini-mental state examination scores of 12\~24 and clinical dementia rating 1 or 2. patients will be allowed to take cholinesterase inhibitors, donepezil, rivastigmine, galantamine or memantine if the dose has been unchanged for the last 3 months before the study entry and remains stable during the 24-week study period. as for the outcome measures, the primary end point will be the score changes of adas-cog at the end of treatment from the baseline. secondary end points include cibic-plus, iadl, behav-ad, mmse and cdr. the statistic analysis will be on both intention-to-treat and completed cases. because of the limitation of the sample size we would expect but a positive trend of the efficacy unless the effect size of dcb-ad1 is larger than 0.63. this information will provide us clue if further clinical investigation such as a phase iii study should be carried out in an even larger scale. we will valuable experience on the adverse effect of prolonged (24-week) use of fo-ti.

Eligibility criteria:
inclusion criteria: 1. male or post menopausal female patients aged ≧50 years old; 2. the informed consent must be signed by the patient and co-signed by their proxy or principal caregivers before undergoing any study procedures; 3. probable alzheimer's disease based on the national institute of neurological and communicative disorders and alzheimer's dementia and related disorder (nincds-adrda) 4. patients with mini-mental state examination (mmse) scores of 12\~24 5. patients with clinical dementia rating (cdr)in mild (cdr = 1) and moderate (cdr = 2) ad 6. cranial computed tomography (ct) or brain magnetic resonance imaging (mri) must be within the past 12 months; 7. patients must be able to complete baseline assessments; 8. an eligible principal caregiver must be able to accompany the patient to all scheduled visits; 9. patients currently taking cheis such as donepezil, rivastigmine, or galantamine are allowed if the dose has been unchanged for the last 3 months before the study entry. exclusion criteria: 1. patients with history of severe systemic disease such as coronary artery disease, myocardial infarct, progressive heart failure, chronic obstructive pulmonary disease within the past 1 year; 2. patients with hepatic and renal insufficiency (alt、ast 3 times above normal range; serum creatinine 2 times above normal range), diabetic patients with poor control of blood sugar (hba1c\>8.5) at study entry; 3. patients with central nervous system disease other than ad such as cerebral vascular disease, parkinson's disease, epilepsy, traumatic brain injury, central nervous system infection, and alcoholic encephalopathy; 4. patients with concurrent psychosis or mood disorder (hamilton depression scale score \> 17); 5. patients diagnosed cancer and treated within the past two years (except for non-invasive skin cancer); 6. patients with general medical conditions, which may confound the results of the study, pose additional risk or preclude evaluation and assessments in this study as judged by the investigator; 7. patients currently treated with any prohibited medications (listed in concomitant treatment section) are not able to fulfill the 2 week-washout period; 8. participation in another study within the last 30 days; 9. females who are within two years of their menopause unless proved not pregnant (determined by urine test); 10. dementia caused by other etiology as indicated by clinically significant abnormal vit b12, folic acid, or thyroid function tests. 11. patients with neurosyphilis confirmed by csf sts/tpha; 12. the neuroimage ct or mri could not be compatible with the diagnosis of probable ad as stated in the nincds criteria; 13. patients with a hachinski score (appendix 5) above 3 are excluded.

Keywords: alzheimer's disease fo-ti chinese herbs